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July 2012 New York City Department of Health and Mental Hygiene Vol.3(3):17-24
 

IN THIS ISSUE

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Preventing and Managing Lyme and Other Tick-borne Diseases
  • Advise patients to use tick checks, DEET, and showers to avoid tick bites; if a tick is attached, it should be removed promptly and safely.

  • Ask patients with suggestive symptoms such as fever, headache, malaise, and/or rash about travel history, as most tick-borne infections are acquired outside of New York City.

  • Follow recommended testing protocols, including repeat testing if indicated, because symptoms may be nonspecific and immune response is often delayed.

 

DIAGNOSIS

The greatest challenges to the differential diagnosis of tick-borne diseases include nonspecific and variable signs and symptoms, such as chills, acute fever, headache, and myalgias, that mimic influenza or other viral illness; delayed antibody response to infected tick bites; and possible coinfection with other diseases.5,10 A single tick bite can transmit multiple pathogens that may result in atypical presentations of tick-borne diseases.11 Many tick bites are painless, and most people will not remember being bitten or notice the bite. Consider the patient's history and known signs and symptoms, which can be diverse in early and later stages and vary widely from person to person.

Signs and Symptoms

Lyme disease: In the early localized stage (3 to 30 days postexposure), 70% to 80% of patients develop erythema migrans (see Figure 2), which is sufficient to diagnose Lyme disease and initiate treatment.10,12 Erythema migrans is not always bull's-eye in appearance, but it does expand in size over time.12

Signs and symptoms of early disease also include fatigue, fever, chills, malaise, headache, myalgias, arthralgias, and lymphadenopathy.12 Erythema migrans is easily distinguished from a minor allergic reaction to a tick or insect bite, which disappears in 1 to 2 days. Erythema migrans gradually expands over a period of several days and can reach up to 12 inches (30 cm) in diameter with areas of clearing near the center of the rash.12 In people of color, erythema migrans can resemble a bruise.13 Consider coinfection with babesiosis, anaplasmosis, or both in patients with more severe initial symptoms, especially high fever for more than 48 hours despite antibiotic therapy, or unexplained leukopenia, thrombocytopenia, or anemia after a tick bite in an endemic area, or in those with no improvement or worsening of systemic symptoms.5 If Lyme disease is left untreated, other symptoms, such as additional erythema migrans (single or multiple lesions), Bell's palsy, meningitis, radiculopathy, carditis (usually AV heart block), and/or myocarditis, may appear days to weeks following exposure.13 Late-stage (months to years postexposure) infections cause articular arthritis with swelling in large joints (especially the knees) affecting one to several joints, peripheral neuropathy, and, rarely, encephalopathy.5,13

About 10% to 20% of patients with Lyme disease have a phenomenon known as post-treatment Lyme disease syndrome (PTLDS), in which mild to moderate symptoms continue for months or years after treatment with antibiotics.14 These symptoms, which can include muscle and joint pains, cognitive defects, sleep disturbance, or fatigue, may be caused by an autoimmune response. There is no evidence that PTLDS is caused by continuing infection. Extending antibiotic therapy past the recommended course is not helpful, and can be harmful for persons with PTLDS.14 Patients may have heard or read about long-term antibiotic therapy for PTLDS. Reassure them that short-course antibiotic therapy is the recommended treatment for Lyme disease.15

Babesiosis (incubation period 1 week to 4 weeks): Signs and symptoms include fever, fatigue, arthralgia, chills, sweats, nonproductive cough, jaundice, and splenomegaly. Babesiosis can be asymptomatic in healthy adults and children. Adults aged 50 years and older and immunocompromised people are at greatest risk for severe disease, which may include severe hemolytic anemia, respiratory distress, pulmonary edema, ecchymosis, petechiae, congestive heart failure, renal failure, and coma.5,16,17 Transmission can also occur via blood transfusion. Consider babesiosis in patients who have received blood products in the preceding 3 months presenting with fever and hemolytic anemia; advise patients who test positive that they can never donate blood or blood products.16

Anaplasmosis (incubation period 1 to 2 weeks): Patients may experience chills, acute fever, headache, and myalgia. Less often seen are nausea, vomiting, diarrhea, cough, arthralgia, stiff neck, and confusion.10,18 In immunosuppressed patients, severe symptoms can include respiratory insufficiency, toxic shock-like illness, rhabdomyolysis, and opportunistic infections.5,10,18 Consider testing for ehrlichiosis as well as anaplasmosis because of the similarities in clinical presentation.

Rocky Mountain spotted fever is a severe infection.19 Patients commonly require hospitalization, and up to 20% of untreated cases and 5% of treated cases have fatal outcomes.10 Early stage (2 to 14 days after a tick bite) symptoms include sudden onset of fever, severe headache, myalgias, chills, malaise, cough, and gastrointestinal symptoms that mimic food-borne illness. A rash often begins within 2 to 5 days, initially as a maculopapular rash on the wrists, ankles, and arms, which then spreads inward to the trunk. The petechial rash (see Figure 1) usually appears on day 5 or 6, although rash may be completely absent in up to 20% of cases.19 Long-term consequences of RMSF can include partial paralysis of the lower extremities, gangrene requiring amputation of digits or limbs, hearing loss, blindness, damage to vital organs, and neurologic deficits.10,18 African American males are at higher risk for serious complications due to a genetic enzyme deficiency.10

Ehrlichiosis (incubation period 7 to 10 days): Symptoms include severe headache, malaise, myalgias, gastrointestinal symptoms, cough, conjunctival injection, arthralgia, and confusion.10,20 A maculopapular rash is present in up to 60% of children and less than 30% of adults. Later-stage symptoms include difficulty breathing or bleeding disorders. Immunosuppressed patients are at highest risk for hospitalization and death.20

Diagnostic Tests

A complete blood cell count or a chemistry panel can be helpful in diagnosing tick-borne infection (see Table 1). During the acute phase of illness, polymerase chain reaction (PCR) tests will confirm anaplasmosis,18 ehrlichiosis,20 and babesiosis,5 but not RMSF10 or Lyme disease.12 This method is most sensitive in the first week of illness (and for the duration of the infection with babesiosis), and rapidly decreases in sensitivity following the administration of appropriate treatment. Treatment should not be withheld due to a pending or negative result, which does not completely rule out the diagnosis.

A blood smear may reveal morulae in the cytoplasm of infected leukocytes with anaplasmosis and ehrlichiosis, or intraerythrocytic parasites with babesiosis.21 Paired-serum serologic testing using indirect immunofluorescence assay (IFA) to diagnose anaplasmosis, ehrlichiosis, and RMSF should be performed on a sample taken soon after the onset of illness and a second sample taken 2 to 4 weeks later.21 Often the initial IgG IFA titer is low, or "negative," and the second shows at least a 4-fold increase in IgG antibody levels. IgM antibodies usually rise at the same time as IgG and remain elevated for months or longer; they are less specific and may result in a false-positive result.

Serologic testing for Lyme disease should follow a 2-step approach. The first step uses an enzyme immunoassay (EIA), and if negative, no further testing is recommended. If the result is positive or equivocal, a Western blot (Wb) should be done. Results are considered positive only if the EIA and Wb are both positive.12,21 Most patients become seropositive within 8 to 12 days of onset of illness, and, therefore, may test negative in the first 1 to 2 weeks following infection. For patients who do not have an erythema migrans rash or who have had signs and symptoms for >1 month, diagnosis should be based on laboratory tests in addition to symptomatology. Patients who have been ill for 1 month or longer (months to years) should test IgG positive by Wb. If such patients are IgG negative, they probably do not have Lyme disease.12,21 See Tick-borne Diseases in the New York City Area: A Physician's Reference Manual for detailed information. Laboratory findings and common tests are given in Table 1.

TABLE 1. BRIEF GUIDE TO DIAGNOSING TICK-BORNE DISEASES5,10,21
Disease Common Findings on Routine Laboratory Tests Diagnostic Findings Notes
Transmitted by black-legged ticks (Ixodes scapularis)
Lyme disease (Borrelia burgdorferi) Elevated ESR, mildly elevated hepatic transaminases (in localized or early disseminated disease); with Lyme disease meningitis, CSF typically has a lymphocytic pleocytosis with slightly elevated protein levels and normal glucose levels. No testing needed if EM is present. Otherwise, do 2-step testing: positive or equivocal EIA test followed by a Western blot test. Patients tested 1 to 2 weeks after onset of illness may be negative due to an absence of detectable antibodies. Rapid initiation of antibiotics may diminish the immune response. For patients with symptoms lasting >1 month, seroconversion to IgG antibodies is expected. For those patients who do not have an EM rash or with signs and symptoms lasting >1 month, make diagnosis based on laboratory tests in addition to symptomatology.
Babesiosis
(Babesia microti)
Decreased hematocrit, elevated reticulocyte counts, elevated ESR, thrombocytopenia, normal or mildly decreased WBC, decreased serum haptoglobin, elevated serum BUN and creatinine, mildly elevated hepatic transaminases, proteinuria, hemoglobinuria Identification of Babesia parasites in a peripheral blood smear (preferred method), or positive PCR assay (preferred method), or serology using IFA may be helpful in patients with a low parasitemia. Blood smear may be negative in infected patients; additional testing is necessary. Intraerythrocytic parasites may be confused with malarial parasites. Transfusion-associated transmission has been reported. Consider babesiosis in patients with febrile illnesses and/or hemolytic anemia who have received blood components in the preceding 3 months.
Anaplasmosis (Anaplasma phagocytophilum) Mild anemia, thrombocytopenia, leukopenia, modest elevations in hepatic transaminases PCR assay during acute illness (preferred method), or 4-fold change in IgG-specific antibody titer by IFA in paired serum samples, or IHC staining of organism, or isolation of organism from a clinical specimen in cell culture DNA testing is particularly important early in the course of illness while bacteria are still present and serologic testing may be negative due to an absence of detectable antibodies. Clinical signs of anaplasmosis and ehrlichiosis are similar. Consider testing for both species.
Transmitted by American dog ticks (Dermacentor variabilis)
Rocky Mountain spotted fever (Rickettsia
rickettsii
)
Anemia, thrombocytopenia, mildly elevated hepatic transaminases, hyponatremia, azotemia Four-fold change in IgG-specific antibody titer by IFA in paired serum samples (preferred method); IHC staining of organism in a biopsy or autopsy specimen, or isolation of organism in cell culture, or detection of DNA in a clinical specimen by PCR assay of tissue specimens (not reliable in blood samples) Tests for IgM antibodies are generally not useful for serodiagnosis of acute disease due to cross-reactivity and persistence of the antibody. Confirmation of the diagnosis is based on laboratory testing, but antibiotic therapy should not be delayed in a patient with a suggestive clinical presentation.
Transmitted by lone star ticks (Amblyomma americanum)
Ehrlichiosis (Ehrlichia chaffeensis) Thrombocytopenia, mild to moderate leukopenia, modest elevations in hepatic transaminases PCR assay during acute illness (preferred method), or 4-fold change in IgG-specific antibody titer by IFA in paired serum samples, or IHC staining of organism, or isolation of organism from a clinical specimen in cell culture DNA testing is particularly important early in the course of illness while bacteria are still present and serologic testing may be negative due to an absence of detectable antibodies. Clinical signs of anaplasmosis and ehrlichiosis are similar, and testing for both species is indicated.

BUN, blood urea nitrogen; CSF, cerebrospinal fluid; EIA, enzyme immunoassay; EM, erythema migrans; ESR, erythrocyte sedimentation rate; IFA, immunofluorescence assay; IgG, immunoglobulin G; IHC, immunohistochemistry; PCR, polymerase chain reaction; WBC, white blood cell.

See Tick-borne Diseases in the New York City Area: A Physician's Reference Manual at www.nyc.gov/html/doh/downloads/pdf/ehs/tick-borne-dx-physician.pdf for detailed information.

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